Pinzon R. T, Veronica V, Christi Y. R. T. D, Pradani R. A. The Effects of Vitamin B Combination Injection on Lymphocyte Count in Chronic Kidney Failure Patients. Biomed Pharmacol J 2020;13(4).

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Manuscript received on :20-Sep-2020
Manuscript accepted on :26-Dec-2020
Published online on: 30-12-2020

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Plagiarism Check: Yes
Reviewed by: Ankur Singh Bist  
Second Review by: Sharad Kamble  
Final Approval by: Omar M. E. Abdel-Salam

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Rizaldy Taslim Pinzon^1*, Vanessa Veronica¹, Yohana Ratih Tirtaningtyas Dian Christi¹, Regina Ayudyaningsari Pradani²

¹Department of Neurology, Faculty of Medicine, Duta Wacana Christian University, Dr. Wahidin Sudirohusodo st. 5-25, Yogyakarta 55224, Indonesia.

²Department of Pharmacy, Sanata Dharma University, Paingan st., Yogyakarta 55281, Indonesia.

Corresponding Author E-mail: drpinzon17@gmail.com

DOI : https://dx.doi.org/10.13005/bpj/2088

Abstract

Background: Chronic kidney failure will lead to decline in immune system. Vitamin B considered has essential roles in immune system, including lymphocyte count. Aims: Measure the effects of vitamin B combination injection on lymphocyte count in chronic kidney failure patients. Methods: This was quasi-experimental study with one group pretest-posttest design from the period of August 2018 - October 2018 at Bethesda Hospital and Panti Rapih Hospital, Yogyakarta, Indonesia. Subjects received vitamin B combination injection (intravenous) after each hemodialysis. Lymphocyte count were measured 3 times namely visit I (before first hemodialysis), visit II (after second hemodialysis), and visit III (after third hemodialysis). Results: The data were obtained from 115 chronic kidney failure patients, consist of 75 male and 40 female. The most common age group in this study was 40-59 years old. There were no significant improvements of lymphocyte counts, both on visit II compared to visit I (1285.713±475.9829/mm³ vs 1504.219±1148.974/mm³; p: 0.065) as well as visit III compared to visit I (1285.713±475.9829/mm³ vs 1315.192±658.6673/mm³; p: 0.766). Conclusion: Vitamin B combination injection has no significant effects on lymphocyte count in chronic kidney failure patients. Intravenous vitamin B was safe for chronic kidney failure patients.

Keywords

Chronic Kidney Failure; Hemodialysis; Immune; Lymphocyte; Vitamin B

Introduction

Chronic kidney failure is defined as abnormalities in renal structure or progressive decline in renal function for more than 3 months¹. Globally, the prevalence of chronic kidney failure in 2016 was 13,4%². Yogyakarta – along with East Nusa Tenggara, South Sulawesi, Lampung, West Java, Central Java, and East Java –  has the third highest stroke cases among provinces in Indonesia³.

Chronic kidney failure and immune system has reciprocal relationship⁴. Various kidney diseases are caused by immune disorders. These kidney diseases will lead to kidney failure. One of the pathomechanisms that strongly related to kidney diseases is deposit of immune complexes in kidneys which will cause inflammatory responses and damages to kidneys⁵. On the other hand, chronic kidney failure will lead to decline in immune system. This will make patients with chronic kidney failure more susceptible to infection than healthy population⁴.

It has long been known that adequate immune system determined by adequate nutrition⁶. Vitamin B considered has essential roles in immune system, including lymphocyte count⁷.

The aim of this study is measuring the effects of vitamin B combination injection on lymphocyte count in chronic kidney failure patients.

Material and Methods

Study Design

This was quasi-experimental study with one group pretest-posttest design. This study was conducted at Bethesda Hospital and Panti Rapih Hospital, Yogyakarta, Indonesia with the period of August 2018 – October 2018.

There were 115 chronic kidney failure patients who met the inclusion and exclusion criteria. Each subject received vitamin B combination injection (intravenous) after each hemodialysis. This vitamin B combination injection consists of 100 mg vitamin B1 (thiamin), 100 mg B6, (pyridoxine) and 500 mcg B12 (cobalamine). Lymphocyte count were measured 3 times namely visit I (before first hemodialysis), visit II (after second hemodialysis), and visit III (after third hemodialysis). Visit II took place 2 weeks after visit I, visit III took place 2 weeks after visit II. There was no control group in this study. Blood sample needed for each examination is as much as 5 mL, stored in a specimen tube containing clot activator.

Subject Selection

Subjects were recruited using consecutive sampling. The inclusion criteria of this study were: (i) Male or female over 18 years old, (ii) Diagnosed with chronic kidney failures and undergo routine hemodialysis (2 times per week) and (iii) Did not use any vitamin B supplementation before. The exclusion criteria were: (i) Hypersensitivity to vitamin B (ii) Participated in other studies and (iii) Subject was pregnant or planned to become pregnant during the study period.

Ethical approval number 906/C.16/FK/2019 was obtained from Duta Wacana Christian University, Yogyakarta, Indonesia. 

Statistical Analysis

Subjects’ characteristics, current medications, and lymphocyte count were evaluated in this study. Subjects’ characteristics and current medications were presented on descriptive analysis. Wilcoxon test was used to analyze lymphocyte count and their relationship with subjects’ current medications. Statistical significance was set at p<0.05.

Results

Table 1: Subjects’ characteristics and current medications.

Table 2: Effects of concomitant medications on lymphocyte counts.

Table 3: Comparison of lymphocyte counts on every visits.

One hundred and fifteen subjects in this study were dominated by male subjects (65.22%). The most common age group in this study was 40-59 years old (51.3%).

Hypertension was the most common comorbid conditions, found in 97 subjects (84.34%). The concomitant medications were 67 (68.26%) calcium channel blocker (CCB), 51 (44.34%) angiotensin II receptor blocker (ARB), 49 (42.61%) diuretic, 9 (7.83%) insulin, 79 (68.69%) calcium carbonate, and 100 (86.96%) folic acid.

Table 2 shows CCB has significant effect on lymphocyte count on visit II compared to visit I (p: 0.03). ARB has significant effect on lymphocyte count on visit II compared to visit I (p: 0.017), also on visit III compared to visit I (p: 0.033). Table 3 shows there were no significant improvements on lymphocyte count before and after vitamin B combination injection, both on visit II compared to visit I (1285.713±475.9829/mm³ vs 1504.219±1148.974/mm³; p: 0.065) as well as visit III compared to visit I (1285.713±475.9829/mm³ vs 1315.192±658.6673/mm³; p: 0.766).

Discussion

Vitamin B effects on immune system are already known. However, the effects of vitamin B combination on immune system, especially lymphocyte count have not been much studied. This study is aimed to identify the effects of vitamin B combination injection on lymphocyte count in chronic kidney failure patients.

Male subjects dominated this study. Previous study showed similar results, there were 0.744 times more male hemodialysis patients than female hemodialysis patients⁸. The most common age group in this study was 40-59 years old (51.3%), consistent with previous study that showed most of hemodialysis patients were between 40-59 years old⁹.

Hypertension is the most common comorbid conditions in this study. This is in line with a research in 2019 which found 85.7% with hypertension as comorbid conditions¹⁰. Hypertension leads to glomerular ischemia that will damage glomerular arteries and arterioles. This mechanism causes and worsens kidney diseases by decreasing glomerular blood flow, impairing kidneys’ structures and functions. Hypertension also damages autoregulation system of kidneys¹¹.

Chronic kidney failure and immune system has reciprocal relationship. Various kidney diseases are caused by immune disorders and chronic kidney failure will lead to decline in immune system. Chronic kidney failure causes damage to kidney structure which causes the body to excrete protein. The excretion of proteins limits the quantity of materials required for composing immune system components, such as antibodies and enzymes⁴.

Lack of micronutrients may lead to immune system dysregulation¹². Vitamin B deficiency is common in patients with chronic kidney failure. Water-soluble vitamins, including vitamin B were wasted during hemodialysis. Other factors, such as minimizing meat consumption, one of vitamin B sources, will reduce vitamin B levels even further¹³.

There were no significant improvements of lymphocyte counts, both on visit II compared to visit I (1285.713±475.9829/mm³ vs 1504.219±1148.974/mm³; p: 0.065) as well as visit III compared to visit I (1285.713±475.9829/mm³ vs 1315.192±658.6673/mm³; p: 0.766). Unlike this study, previous study in Wadsworth showed significant lymphocyte count improvement (p<0.05) in 8 hemodialysis patients after administration of vitamin B6 supplementation¹⁴. Another studies involving elderly persons and young women consuming a controlled diet showed vitamin B6 supplementation has significant effects on lymphocyte proliferation^15,16. A study in 2008 found significant improvement of lymphocyte percentage after vitamin B12 supplementation¹⁷. These differences might be due to only vitamin B6 and vitamin B12 has direct effects on lymphocyte counts, while vitamin B1 does not have direct effect on lymphocyte counts. Innate and adaptive immunity were affected by vitamin B6 deficiency, including T-lymphocytes proliferation and function. Furthermore, vitamin B6 associated with cellular immune activation mediated by IFN-gamma¹⁸. Immune sytem regulation, immunomodulator, and involved in cell division were 3 main roles of vitamin B in immune system. Decreased levels of vitamin B12 will decrease cytotoxic T cells levels¹⁹. Vitamin B12 also helps body use folate. Folate deficiency causes immunodeficiency with T-lymphocyte proliferation impairment²⁰. Vitamin B1 main roles in immune response are its antioxidative effect and inhibit oxidative stress stimulation of NF- κB⁷.

Concomitant medications might affect the identification of vitamin B combination injection effects on lymphocyte counts. There were 2 antihypertensive medications CCB has significant effect on lymphocyte count visit II compared to visit I (p: 0.03). ARB has significant effect on lymphocyte count on visit II compared to visit I (p: 0.017), also on visit III compared to visit I (p: 0.033). CCBs are known as inhibitor of phytohemagglutinin (PHA)-induced proliferation of human lymphocytes²¹. ARBs inhibit angiotensin II receptor (AGT1R) signaling, an important part for lymphocyte, especially T-lymphocyte activation²². Thus, antihypertensive medications effects work against vitamin B effects on immune system.

The limitations of this study were: there was no control group in this study and confounding factors did not well-evaluated.

Conclusions

Vitamin B combination injection has no significant effects on lymphocyte count in chronic kidney failure patients. Intravenous vitamin B was safe for chronic kidney failure patients.

Acknowledgment

This research was fully funded by the authors.

Conflict of Interest

There are no conflict of interest.

References

1. Dipiro J. T. Pharmacotherapy Handbook, 9^th Edition. McGraw Hill, New York 2015: 787.
   CrossRef
2. Hill N. R, Fatoba S. T, Oke J. L, Hirst J. A, O’Callaghan C. A, Lasserson D. S, et al. Global Prevalence of Chronic Kidney Disease – A Systematic Review and Meta-Analysis. PLoS ONE, 2016; 11(7): e0158765.
   CrossRef
3. Indonesian Ministry of Health. Basic Health Research. Health Research and Development Agency, Jakarta 2013: 95.
   CrossRef
4. Imig J. D and Ryan M. J. Immune and inflammatory role in renal disease. Compr Physiol, 2013; 3: 957-976.
   CrossRef
5. Heeringa S. F and Cohen C. D. Kidney diseases caused by complement dysregulation: acquired, inherited, and still more to come. Clin Dev Immunol, 2012; 2012: 695131.
   CrossRef
6. Chandra R. K. Nutrition and the immune system from birth to old age. Eur J Clin Nutr, 2002; 56: S73-S76.
   CrossRef
7. Spinas E, Saggini A, Kritas S. K, Cerulli G, Caraffa A, and Antinolfi P. Crosstalk between vitamin B and immunity. Journal of Biological Regulators & Homeostatic Agents, 2015; 29(2): 283-288.
   CrossRef
8. Hecking M, Bieber B. A, Ethier J, Kautzky-Willer A, Sunder-Plassmann G, Säemann M. D, et al. Sex-specific differences in hemodialysis prevalence and practices and male-to-female mortality rate: the Dialysis Outcomes and Practice Patterns Study (DOPPS). PLoS medicine, 2014; 11(10): e1001750.
   CrossRef
9. Bayhakki B and Hasneli Y. Relationship between Length of Undergoing Hemodialysis and Inter-Dialytic Weight Gain (IDWG) in Hemodialysis Patients. Jurnal Keperawatan Padjadjaran, 2017; 5(3): 242-248.
   CrossRef
10. Pinzon R. T, Wijaya B. M, Pramudita E. A, Wuryaningsih N. S and Sujatno P. Prevalence of elevated levels of homocysteine (hyperhomocysteinemia) in patients with chronic kidney disease undergoing hemodialysis. J Clin Med Kaz, 2019; 3(53): 21-25.
    CrossRef
11. Abraham G, Arun K, Gopalakrishnan N, Renuka S, Pahari D. K and Deshpande P. Management of hypertension in chronic kidney disease: Consensus statement by an expert panel of Indian nephrologists. Journal of The Association of Physicians of India,  2017; 65(2): 6-22.
12. Bull S. J, Huezo-Diaz P, Binder E. B, Cubells J. F, Ranjith G, Maddock C, et al. Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment. Mol Psychiatry, 2009; 14: 1095-1104.
    CrossRef
13. Menon V, Wang X, Greene T, Beck G. J, Kusek J. W, Selhub J, et al. Homocysteine in chronic kidney disease: Effect of low protein diet and repletion with B vitamins. Kidney International, 2005; 67: 1539-1546.
    CrossRef
14. Casciato D. A, McAdam L. P, Kopple J. D, Bluestone R, Goldberg L. S, Clements P. J, et al. Immunologic Abnormalities in Hemodialysis Patients: Improvement after Pyridoxine Therapy. Nephron, 1984; 38: 9-16.
    CrossRef
15. Talbott M. C, Miller L. T and Kerkvliet N. I. Pyridoxine supplementation: effect on lymphocyte responses in elderly persons. The American Journal of Clinical Nutrition,  1987; 46(4): 659-664.
    CrossRef
16. Kwak H, Hansen C. M, Leklem J. E, Hardin K and Shultz T. D. Improved Vitamin B-6 Status Is Positively Related to Lymphocyte Proliferation in Young Women Consuming a Controlled Diet. The Journal of Nutrition, 2002; 132(11): 3308-3313.
    CrossRef
17. Erkurt M. A, Aydogdu I, Dikilitaş M, Kuku I, Kaya E, Bayraktar N, et al. Effects of Cyanocobalamin on Immunity in Patients with Pernicious Anemia. Med Princ Pract,  2008; 17: 131-135.
    CrossRef
18. Christensen M. H. E, Pedersen E. K. R, Nordbø Y, Varhaug J. E, Midttun Ø, Ueland P. M, et al. Vitamin B6 Status and interferon-γ-mediated Immune Activation in Primary Hyperparathyroidism. J Intern Med, 2012; 272(6): 583-591.
    CrossRef
19. Mikkelsen K, Stojanovska L, Prakash M and Apostolopoulos V. The effects of vitamin B on the immune/ cytokine network and their involvement in depression. Maturitas,  2017; 96: 58-71.
    CrossRef
20. Kishimoto K, Kobayashi R, Sano H, Suzuki D, Maruoka M, Yasuda K, et al. Impact of Folate Therapy on Combined Immunodeficiency Secondary to Hereditary Folate Malabsorption. Clin Immunol, 2014; 153(1): 17-22.
    CrossRef
21. Weir M. R, Peppler R, Gomolka D and Handwerger B. S. Calcium channel blockers inhibit cellular uptake of thymidine, uridine and leucine: the incorporation of these molecules into DNA, RNA and protein in the presence of calcium channel blockers is not a valid measure of lymphocyte activation. Immunopharmacology, 1993; 25(1): 75-82.
    CrossRef
22. Tawinwung S, Petpiroon N and Chanvorachote P. Blocking of Type 1 Angiotensin II Receptor Inhibits T-lymphocyte Activation and IL-2 Production. In Vivo,  2018; 32(6): 1353-1359.
    CrossRef